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ADAM and ADAMTS Family of Metalloproteinases: Role in Cancer Progression and Acquisition of Hallmarks

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Proteases in Human Diseases

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Abstract

The adamalysins, which include the ADAMs and ADAMTSs, are multidomain, multifunctional proteins of the metzincin superfamily of zinc-dependent metalloproteinases that play a key role in extracellular matrix remodeling and regulation of the tissue microenvironment. While ADAMs are mostly membrane-anchored proteinases, the ADAMTSs are secreted proteinases and/or adhesion molecules. A major function of the ADAMs is ectodomain shedding of membrane-bound growth factors, receptors, cytokines, chemokines, and proteoglycans. The adamalysins are also involved in a multitude of biological processes including fertilization, organogenesis, hemostasis, cell adhesion, intracellular signaling, angiogenesis, and ECM assembly and turnover. These metalloproteinases exert both promoting and inhibitory effects on tumorigenesis and serve as biomarkers of cancer progression and prognosis. Dysregulated expression of adamalysins leads to acquisition of cancer hallmarks such as increased cell proliferation, apoptosis evasion, migration, neovascularization, invasion, and metastasis. In addition, aberrant expression of these proteases also results in drug resistance. Of late, the adamalysins have emerged as potential molecular targets for cancer therapeutics. This chapter summarizes current knowledge on the different types of ADAMs and ADAMTSs, their general structure, functions, role in cancer progression, and acquisition of major cancer hallmarks as well as their potential as diagnostic and prognostic aids and therapeutic targets based on available literature.

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  1. Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, 835205, Jharkhand, India

    Rajakishore Mishra

  2. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Chidambaram, 608002, Tamil Nadu, India

    Siddavaram Nagini

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  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Tapati Chakraborti

  3. Department of Physiology, Faculty of Medicine, St. Boniface General Hospital, Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Mishra, R., Nagini, S. (2017). ADAM and ADAMTS Family of Metalloproteinases: Role in Cancer Progression and Acquisition of Hallmarks. In: Chakraborti, S., Chakraborti, T., Dhalla, N. (eds) Proteases in Human Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-10-3162-5_15

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